HOPE to Reduce Tumour Recurrence After LT In Patients With HCC

Trial Title: HOPE to Reduce Tumour Recurrence After LT In Patients With HCC

NCT ID: NCT05876052

Condition: Liver Cancer
Tumor Recurrence
Hepatocellular Carcinoma
Liver Transplantation
Ex-vivo Hypothermic Perfusion

Conditions: Official terms:
Recurrence
Hypothermia

Study type: Interventional

Study phase: N/A

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Device
Intervention name: Hypothermic oxygenated Perfusion - HOPE
Description: HOPE will start by flushing the organ at low flow values (30 ml/min) with new oxygenated perfusion fluid during back-table preparation. Organ will be treated with continuous HOPE until transplant. Organ perfusion will be continuously monitored. Minimal perfusion time will be 1 hour for livers.
Arm group label: Hypothermic oxygenated Perfusion - HOPE

Summary: Hypothermic oxygenated ex-situ machine perfusion (HOPE) is a dynamic preservation method that has been developed to reduce the incidence and severity of ischaemia-reperfusion injury and to improve outcomes after liver transplantation. Whit this study Pi and collaborators hypothesize that the application of ex-situ liver perfusion before LT in HCC recipients leads to an optimization of graft function, with a decrease in ischaemia-reperfusion injury and a possible decrease in tumor cell growth. This is multicentre, prospective, two-arm, randomized, controlled, clinical trial, that will will involve patients with HCC candidate to LT. The liver grafts will be randomized in two groups to compare HOPE and static cold storage (SCS) preservation before transplantation. For each group evaluation of clinical outcomes, graft function tests, histologic findings, perfusate, tumor characteristics, and recurrence will be done.

Detailed description: Tumor recurrence after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is a major complication leading to decreased long-term survival of patients. However, the mechanisms leading to tumor emergence and growth remain incompletely understood. Several factors, can promote cancer growth or recurrence. Ischemia-reperfusion injury (IRI) has been recognized as an important early driver of microvascular dysfunction resulting in tissue hypoxia and inflammation, which promotes tumor cell growth. A recent therapeutic strategy used to reduce the incidence and severity of IRI and to improve outcomes after transplantation is ex vivo HOPE. Which allows to redirect anaerobic metabolism to aerobic metabolism under hypothermic conditions, protect grafts from oxidative species-related damage, improve graft function and may potentially reduce cancer recurrence after liver transplantation. A multicentre, prospective, two-arm, randomized, controlled, clinical trial will be performed; four Italian centres (Bologna, Palermo, Pisa e Torino) will be involved. A total of 192 patients with a history of HCC or active HCC, already present or about to be placed in the liver transplantation waiting list of the four transplantation center will be enroll. The liver grafts will be randomized in two groups to compare HOPE and SCS preservation before transplantation. For each group evaluation of clinical outcomes, graft function tests, histologic findings, perfusate, tumor characteristics, and recurrence will be done during follow up visit; 1-3-6 and 12 months after transplantation. Livers assigned to HOPE group will be perfused by machine perfusion with cold Belzer solution (4°-10°C) and with continuous oxygenation (partial pressure of oxygen = 500-600 mmHg). Organs will be perfused from the start of the back-table procedure until implantation, without increasing cold ischemia time (CIT). In the control group livers undergoing SCS will be steeped in cold Celsior or Belzer solutions and stored in ice. Presence of bacterial and/or fungal contamination will be tested by setting up microbiological cultures from the preservation fluid, before and after treatment in both groups.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - all patients with HCC medical history or active HCC - Donation after circulatory death (DBD) donor with standard or extended criteria Exclusion Criteria: - Living transplantation - Split Transplantation - Combined Transplantation - Donation after cardiac death (DCD)Transplantation - Re-transplantation - Patient whose liver graft will undergo ex-vivo machine perfusion for medical decision, regardless the study

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Address:
City: Bologna
Zip: 40138
Country: Italy

Start date: May 2023

Completion date: May 2025

Lead sponsor:
Agency: University of Bologna
Agency class: Other

Collaborator:
Agency: Azienda Ospedaliero, Universitaria Pisana
Agency class: Other

Collaborator:
Agency: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
Agency class: Other

Collaborator:
Agency: A.O.U. Città della Salute e della Scienza
Agency class: Other

Collaborator:
Agency: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Agency class: Other

Source: University of Bologna

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05876052